{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T12:28:33Z","timestamp":1785932913627,"version":"3.56.0"},"reference-count":97,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a severe form of pulmonary hypertension with poor prognosis. It most commonly arises in systemic sclerosis (SSc), followed by systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Its pathogenesis involves a complex interplay of immune dysregulation, chronic inflammation, endothelial injury, vascular remodeling, and fibrosis. Although vasodilators targeting the endothelin, nitric oxide, and prostacyclin pathways remain the therapeutic backbone, newer agents\u2014including the activin signal inhibitor sotatercept and inhaled treprostinil\u2014have expanded treatment options. Immune-targeted therapies such as glucocorticoids, cyclophosphamide, mycophenolate mofetil, rituximab, and IL-6 receptor inhibitors may benefit inflammation-dominant PAH phenotypes, while fibrotic phenotypes continue to demonstrate limited responsiveness. In addition to brain natriuretic peptide (BNP), N-terminal (NT)-proBNP and disease-specific autoantibodies, emerging biomarkers show promise for early detection, risk stratification, and personalized treatment, though validation in CTD-PAH is lacking. Advances in animal models replicating immune-mediated vascular injury and fibrosis have further improved mechanistic understanding. Despite these developments, substantial unmet needs remain, including the absence of disease-specific therapeutic strategies, limited biomarker integration into clinical practice, and a scarcity of large, well-designed trials targeting individual CTD subtypes. Addressing these gaps will be essential for improving prognosis in patients with CTD-PAH.<\/jats:p>","DOI":"10.3390\/biom16010140","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T09:27:12Z","timestamp":1768296432000},"page":"140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: Current Therapeutic Strategies and Future Prospects"],"prefix":"10.3390","volume":"16","author":[{"given":"Yukina Mizuno","family":"Yokoyama","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan"},{"name":"Department of Rheumatology, Daido Hospital, Nagoya 457-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-5296","authenticated-orcid":false,"given":"Ryu","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2576-9409","authenticated-orcid":false,"given":"Tomohiro","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuhei","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayu","family":"Shiomi","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Katsushima","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8576-5816","authenticated-orcid":false,"given":"Kazuo","family":"Fukumoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Haji","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Daido Hospital, Nagoya 457-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1801887","DOI":"10.1183\/13993003.01887-2018","article-title":"Pathology and pathobiology of pulmonary hypertension: State of the art and research perspectives","volume":"53","author":"Humbert","year":"2019","journal-title":"Eur. 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